In the preliminary antitumor evaluation, 1-Beta-D-arabinofuranosylcytosine 5'-diphosphate-5-L-1,2-dipalmitin (ara-CDP-L-dipalmitin) elicited promising therapeutic results against both i.p. and i.c. implanted L1210 lymphoid leukemia in mice, exceeding those of ara-C alone and combination of ara-CMP and L-Alpha-dipalmitoylphosphatidic acid. The conjugate also showed a remarkable antitumor activity against ara-C resistant L1210 in mice. Thus, as a more convincing argument for development of this conjugate would be to determine its activity against various ara-C resistant tumors. This proposal is: 1) for synthesis of ara-CDP-dipalmitin in sufficient quantity and purity to perform the in vivo testing; 2) for evaluation of in vivo antitumor activity in ara-C resistant L1210 leukemia sublines and other ara-C resistant tumor models (P388/ara-C, 36/ara-C, HL-60/ara-C, etc); 3) for evaluation of antitumor activity against other animal tumor models and comparison of its activities with those of the reference depot forms (5'-O-palmitoyl-ara-C and N4-palmitoyl-ara-C); 4) depending on the outcome of these initial studies, for studies on its mechanism of action and related pharmacologic aspects using 3H and 14C double labeled conjugate. Ara-CDP-L-dipalmitin will be synthesized by condensation of ara-CMP morpholidate and L-Alpha-dipalmitoylphosphatidic acid. The latter will be prepared chemically from D-mannitol. Sonicated solution of the conjugate in 0.9% NaCl will be used for the antitumor evaluation according to the procedure outlined in the NCI Protocol for Screening and the activity will be compared with those of the reference depot forms of ara-C. The other animal tumor models will include Lewis lung carcinoma, murine B16 melanoma and colon 26-carcinoma. [5-3H] -Ara-CDP-L-1,2-di[1-14C] palmitin will be synthesized by condensation of [5-3H] -ara-CMP morpholidate and L-Alpha-di[1-14C] palmitoylphosphatidic acid. The latter compound will be prepared from enzymatic hydrolysis of L-Alpha-di[1-14C] palmitoylphosphatidyl choline with phospholipase D. The labeled conjugate will then be incubated with L1210/0 or L1210/ara-C lymphoid leukemia cells in culture and its cellular uptake, transport, and metabolism will be studied. Pharmacokinetics and metabolism of the conjugate in mice will be also studied.